Phenylalanine (abbreviated as Phe or F)[1] is an α-amino acid with the formula HO2CCH(NH2)CH2C6H5, which is found naturally in the breast milk of mammals and manufactured for food and drink products and are also sold as nutritional supplements for their reputed analgesic and antidepressant effects. Phenylalanine is structurally closely related to dopamine, epinepherine (adrenaline) and tyrosine.

The genetic disorder phenylketonuria (PKU) is the inability to metabolize phenylalanine. Individuals with this disorder are known as "phenylketonurics" and must abstain from consumption of too much phenylalanine. This dietary restriction also applies to pregnant women with hyperphenylalanine (high levels of phenylalanine in blood) because they do not properly metabolize the amino acid phenylalanine. Persons suffering from PKU must monitor their intake of protein to control the buildup of phenylalanine as their bodies convert protein into its component amino acids.

A non food source of phenylalanine is the artificial sweetener aspartame. This compound, sold under the trade names "Equal" and "NutraSweet", is metabolized by the body into several chemical byproducts including phenylalanine. The breakdown problems phenylketonurics have with protein and the attendant build up of phenylalanine in the body also occurs with the ingestion of aspartame, although to a lesser degree. Accordingly, all products in Australia, the U.S. and Canada that contain aspartame must be labeled: "Phenylketonurics: Contains phenylalanine." In the UK, foods containing aspartame must carry ingredients panels that refer to the presence of "aspartame or E951" [3] and they must be labeled with a warning "Contains a source of phenylalanine." These warnings are specifically placed to aid individuals who suffer from PKU so that they can avoid such foods.

Geneticists have recently sequenced the genome of macaques. Their investigations have found "some instances where the normal form of the macaque protein looks like the diseased human protein" including markers for PKU.[4]

DL-Phenylalanine is marketed as a nutritional supplement for its supposed analgesic and antidepressant activities. The reputed analgesic activity of DL-phenylalanine may be explained by the possible blockage by D-phenylalanine of enkephalindegradation by the enzymecarboxypeptidase A.[5] The mechanism of DL-phenylalanine's supposed antidepressant activity may be accounted for by the precursor role of L-phenylalanine in the synthesis of the neurotransmitters, norepinephrine and dopamine. Elevated brain levels of norepinephrine and dopamine are thought to have an antidepressant effect.[How to reference and link to summary or text] Following ingestion, D-Phenylalanine is absorbed from the small intestine and transported to the liver via the portal circulation. A small amount of D-phenylalanine appears to be converted to L-phenylalanine. D-Phenylalanine is distributed to the various tissues of the body via the systemic circulation. It appears to cross the blood-brain barrier less efficienciently than L-phenylalanine, and so a small amount of an ingested dose of D-phenylalanine is not absorbed but excreted in the urine.

The genetic codon for phenylalanine was first discovered by J. Heinrich Matthaei and Marshall W. Nirenberg in 1961. They showed that by using m-RNA to insert multiple uracil repeats into the bacterium E. coli, the bacterium produced a new protein consisting solely of repeated phenylalanine amino acids. This discovery lead to the determination of the relationship between RNA and amino acids, which was foundational to the understanding of the Genetic Code.

Phenylalanine is contained in many foodstuffs and byproducts. Many products are advertised as containing this ingredient including the soft drink 'lilt' to name but one.